Treating precancerous anal lesions in people with HIV reduced their risk of developing anal cancer by more than half compared with active monitoring, according to results from the ANCHOR study.
In the randomized phase III trial of more than 4,500 individuals with anal high-grade squamous intraepithelial lesions (HSIL), nine of those assigned to treatment with office-based electrocautery eventually developed anal cancer versus 21 who underwent active monitoring, resulting in a statistically significant 57% reduction in the risk of anal cancer over a 25.8-month follow-up (P=0.03), reported Joel Palefsky, MD, of the University of California San Francisco, and colleagues.
The number of cancer cases reported in the two treatment groups translated into an anal cancer incidence rate of 173 per 100,000 person-years (95% CI 90-332) with treatment versus 402 per 100,000 person-years (95% CI 262 to 616) with monitoring, they stated in the New England Journal of Medicine.
“We found for the first time that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” Palefsky said during a press briefing. “We believe the data should result in inclusion of screening for and treating anal HSIL as standard care in people living with HIV.”
Cumulative incidence of progression to anal cancer at 4 years was 0.9% in the treatment group and 1.8% in the monitoring group.
Palefsky noted that, in the treatment arm, there were “more treatment failures than we would have liked.” While there were eight serious adverse events (AE) reported (seven in the treatment arm; one in the monitoring arm), overall the treatments provided “were safe and well tolerated,” Palefsky said, adding that his group will continue to analyze study data to determine others issues such as as cost-effectiveness. “The data are strongly supportive of inclusion in standard of care for this procedure,” he said.
However, ANCHOR “is not a screening study,” Palefsky cautioned.
“We weren’t trying to figure out the best way to screen for anal HSIL, because we didn’t know whether it was worth doing so,” he said. “Now that we know that treating anal HSIL does reduce cancer, we do believe that screening for this lesion is now important.”
Anal cancer is caused by human papillomavirus (HPV) infection, particularly HPV16, and is preceded by an HSIL, also known as anal intraepithelial neoplasia.
While the incidence of anal cancer is rare, it has been increasing in the U.S. and other developed countries since the 1970s, particularly among persons living with HIV, with rates that “are unacceptably high,” said Robert Yarchoan, MD, director of National Cancer Institute Office of HIV and AIDS Malignancy, at the press briefing.
Moreover, persons living with HIV have a high prevalence and incidence of anal HPV infection and anal HSIL, consistent with their elevated risk of anal cancer, observed Palefsky and colleagues. Palefsky pointed out that people with HIV are getting older, which is “particularly concerning given that the cancers we’re talking about here become more common as people age.”
“Anal cancer is very similar to cervical cancer,” Yarchoan noted. “We know that treating cervical HSIL can reduce cervical cancer, but it was not known if treating anal HSIL would prevent anal cancer. And with this increase [in anal cancer] there was a real interest in doing something about it.”
“The only way to determine whether it really worked was to do a large randomized trial,” he added, which led to ANCHOR, conducted through the AIDS Malignancy Consortium.
ANCHOR was performed at 25 sites in the U.S. in persons living with HIV (median age 51; 80% male; 42% Black), who were invited to undergo HSIL screening with high-resolution anoscopy (HRA). If the investigators saw signs of high-grade disease, a biopsy of tissue sample was done. Those with biopsy-proven high-grade disease were randomized 1:1 to active monitoring with or without treatment.
In the treatment group, the initial approach was office-based electrocautery ablation (primarily hyfrecation) in 83.6%, infrared coagulation in 4.8%, ablation or excision under anesthesia in 2.3%, topical fluorouracil in 4.5%, and topical imiquimod in 0.5%. The authors explained that over the course of the trial, 86.3% were treated with one therapeutic method, 10.5% had two methods, and the rest were treated with three or more.
Serious AEs that were deemed related to treatment included infection or abscess due to anal biopsy (two in the treatment arm and one in the monitoring arm). There were 55 deaths in the treatment arm and 48 in the monitoring arm, but none “were determined … to be related to trial interventions,” the authors stated.
Palefsky said questions that still need answers are whether the study results can be extended to other at-risk populations — persons with immunosuppression for solid-organ transplantation; women with a history of vulvar or cervical HSIL or cancer, for example — and how to screen for HSIL, as screening HRA is expense and operator-dependent.
“It takes a very long time to get good at it,” he said. “So we need to optimize screening algorithms to find people with HSIL most efficiently for referral for HRA, such as what we already do in the cervix, for example (cytology or Pap smears and HPV testing). So this is an area of future research. And we also need to scale up our HRA training programs so that we have enough providers skilled in HRA to meet the need.”
The study was supported by the NCI.
Palefsky disclosed relationships with Antiva Biosciences, Merck, Vir Biotechnology, and Virion Therapeutics. Co-authors disclosed multiple relationships with industry.